IMNM

iPSC and Mouse Neurocardiac Models (NS090364)

Specific Aims and Tasks

This core aims to determine whether heart rhythm disturbances are a cause of
Sudden Unexplained Death in Epilepsy (SUDEP) in Dravet Syndrome, a severe childhood epilepsy with a high
risk of SUDEP. The proposed studies involve a unique combination of experiments using patient-derived heart
cells and neurons, mouse models, and patient electrocardiogram data obtained before, during and after
seizures. Progress in these Aims will complement and synergize with the other projects in this
proposal to not only uncover SUDEP mechanisms in Dravet Syndrome that will likely be applicable to other
severe epilepsies, but also to provide advances in identifying biomarkers to define at-risk patients.
Utilize iPSC-derived cardiac myocytes and autonomic neurons as well as mouse models to determine whether heart rhythm disturbances are a cause of SUDEP in Dravet Syndrome, a severe childhood epilepsy with a high risk of SUDEP

Focus on SCN1A and SCN1B mutations and investigation of their effect on cardiac and autonomic neuron excitability